Abstract
1. The haemodynamic effects of S-12968-(-), a new dihydropyridine calcium entry blocker (enantiomer of S-11568), were compared with those of the stereoisomer, S-12967-(+), nifedipine, and sodium nitroprusside. 2. A first experiment was performed in conscious, young male rats chronically implanted with femoral artery and vein cannula and repeated in rats previously treated with vitamin D3 and nicotine. Such treatment produces marked vascular calcium overload, especially of the compliance arteries, with no overt sign of toxicity as far as can be judged from the plasma profile. 3. In conscious rats the hypotensive effects of S-12968-(-), nifedipine and sodium nitroprusside were of similar potency. The falls in blood pressure produced by nifedipine and sodium nitroprusside were accompanied by reflex tachycardia which was less marked in the vascular calcium overload model. S-12968-(-) did not induce reflex tachycardia. S-12967-(+) increased blood pressure in both models. 4. A second experiment was performed in open-chest pentobarbitone-anaesthetized rats with electromagnetic flowprobes on the ascending aorta. In controls the falls in blood pressure produced by low doses (0.1 and 0.3 mg kg-1, i.v.) of S-12968-(-) were accompanied by falls in total peripheral resistance. The higher dose (1 mg kg-1, i.v.) of S-12968-(-) produced no change in total peripheral resistance, and in rats pretreated with vitamin D3 and nicotine, cardiac output fell. 5. In conclusion, S-12968-(-) appears to have a dual action and to lower blood pressure at higher doses at least in part by a cardiac effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Henrion D., Chillon J. M., Godeau G., Muller F., Capdeville-Atkinson C., Hoffman M., Atkinson J. The consequences of aortic calcium overload following vitamin D3 plus nicotine treatment in young rats. J Hypertens. 1991 Oct;9(10):919–926. [PubMed] [Google Scholar]
- Kiowski W., Erne P., Bertel O., Bolli P., Bühler F. Acute and chronic sympathetic reflex activation and antihypertensive response to nifedipine. J Am Coll Cardiol. 1986 Feb;7(2):344–348. doi: 10.1016/s0735-1097(86)80503-4. [DOI] [PubMed] [Google Scholar]
- Prieto D., Mulvany M. J., Nyborg N. C. (+)-S-12967 and (-)-S-12968: 1,4-dihydropyridine stereoisomers with calcium channel agonistic and antagonistic properties in rat resistance arteries. Br J Pharmacol. 1991 Jul;103(3):1703–1708. doi: 10.1111/j.1476-5381.1991.tb09850.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Randle J. C., Lombet A., Nagel N., Abraham C., Aptel H., Peglion J. L., Renaud J. F. Ca2+ channel inhibition by a new dihydropyridine derivative, S11568, and its enantiomers S12967 and S12968. Eur J Pharmacol. 1990 Nov 6;190(1-2):85–96. doi: 10.1016/0014-2999(90)94115-e. [DOI] [PubMed] [Google Scholar]
- Sassen L. M., Van der Zande J., McFalls E. O., Verdouw P. D. Cardiovascular profile of the new dihydropyridine derivative S12968. Eur J Pharmacol. 1991 Jun 18;199(1):61–67. doi: 10.1016/0014-2999(91)90637-6. [DOI] [PubMed] [Google Scholar]